Acute Respiratory Failure
Conditions
Keywords
sedation strategy, mechanical ventilation, ventilator weaning
Brief summary
A three-arm, randomized, pilot study, to assess the feasibility for the analgesia-first sedation (AFS) study arm/intervention (Fentanyl push first). The study will assess additional outcomes for all three (3) validated strategies for sedation and pain management.
Detailed description
A three-arm, randomized, pilot study, to assess the feasibility for the analgesia-first sedation (AFS) study arm/intervention (Fentanyl push first). The study will assess additional outcomes for all three (3) validated strategies for sedation and pain management. A significant proportion of patients admitted to the intensive care unit (ICU) require mechanical ventilation (MV). To maintain comfort and facilitate quality care, large quantities of sedatives and analgesics are often administered either by continuous infusion, with or without daily interruption (DI) of sedation, or as intermittent doses of analgesics. Three validated sedation strategies are currently available. A recently published study ( trial has shown that instituting protocol-directed sedation in patients requiring continuous infusion of sedatives and analgesics, whether or not daily interruption (DI) of the sedative occurs, will improve MV outcomes, specifically the duration of MV. Girard et al performed a randomized, multicenter, clinical trial (ABC- Awakening and Breathing Controlled trial) evaluating the pairing of a spontaneous awakening trial (SAT) with an SBT. Most recently, a Danish study by Strom et al. investigated whether an analgesia-first approach to patient comfort that consisted of intermittent doses of intravenous opioids, and the initiation of IV sedation for short periods only when acute agitation was present, would be superior to a protocol similar to the ABC trial. While the three above mentioned approaches are accepted and currently implemented in the critical care community there is no comparative study or evaluation on the optimal timing to conduct a spontaneous breathing trial (SBT) for assessing weaning readiness with each of these strategies. It is possible that a SAT strategy, where sedative and opioid infusions are interrupted, may lead to more agitation and anxiety than a strategy in patients managed with a sedation protocol where intravenous sedative and analgesic therapy is regularly titrated to maintain patients in a lightly sedated state. Moreover, it remains unclear whether analgesia-first strategy (AFS) is feasible and if there are advantages of AFS (Fentanyl push first interventions) over either an SAT or sedation protocol strategy in terms of the time it takes to wean patients from MV or ICU length of stay. However, it is noteworthy to mention that the analgesia-first strategy was associated with more delirium episodes, which were attributed to the ability to assess for it in a more awake patient. However, comparing delirium occurrence in studies with different sedation goals and methodologies may be inaccurate. The investigators therefore propose a three-arm, randomized clinical trial. This pilot study will measure feasibility for the implementation of analgesia-first sedation (AFS) study arm/intervention (Fentanyl push first). The study will assess additional outcomes for all three (3) validated strategies for sedation and pain management.
Interventions
DRUGSedation Protocol with Daily Interruption
Continuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning both infusions are stopped and when the patient is awake and met the SBT safety screen, 120-min CPAP trial is performed. If the patient meets the CPAP passing criteria, arterial blood gas (ABG) is done and the patient is placed back to the previous ventilator setting. ABG result is notified to the physician for determination for extubation. If the patient does not pass the CPAP trial it is repeated next morning.
DRUGSedation Protocol Without Daily Interruption
Continuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen, 120-min CPAP trial is performed. If the patient meets the CPAP passing criteria, arterial blood gas (ABG) is done and the patient is placed back to the previous ventilator setting. ABG result is notified to the physician for determination for extubation. If the patient does not pass the CPAP trial it is repeated next morning.
DRUGFentanyl Push First
Fentanyl 25 mcg intravenous push (IVP) every 5 min up to 4 doses hourly as needed to target pain score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when patient's RASS is 0 to -2 and passes the SBT safety screen, 120-min CPAP trial is performed. If patient meets CPAP passing criteria, the physician will be notified for determination of extubation. If patient does not pass, it is repeated next morning. If target RASS is not achieved with fentanyl IV push alone, study team is notified and fentanyl infusion at 50 mcg/hr titrated by 25 mcg/hr every 30 min to target pain score (max 6 hrs). If target RASS score is not achieved with the fentanyl IV, propofol infusion is started at 5 mcg/kg/hr titrated by 5 mcg/kg/hr every 15 min to target RASS score (max 6 hrs).
Sponsors
Memorial Medical Center Foundation
MemorialCare Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥ 18 years of age 2. Mechanically ventilated with an expected duration of MV ≥ 48 hours 3. ICU team has initiated continuous sedative and/or /analgesic infusions
Exclusion criteria
1. Admission after resuscitation from cardiac arrest 2. Admission with traumatic brain injury or another acute neurologic event (e,g. stroke, uncontrolled seizures). 3. History of severe dementia 4. Admission because of acute alcohol withdrawal or acute drug intoxication 5. Administration of more than 24 hours of continuous sedation 6. Allergy to fentanyl, midazolam, and/or propofol 7. Lack of informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study Feasibility | Up to 28 days | Study feasibility for all 3 Arms/Groups (i.e., Fentanyl Push First, Sedation Protocol Without Interruption, and Sedation Protocol with Interruption) being greater than or equal to 80% and protocol feasibility was based on protocol compliance (total percentage of study days participants were compliant with protocol). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU Length of Stay | Up to 28 days | Duration of ICU stay at 28 days |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mechanical Ventilation Free Days | Up to 28 days | This is clinical outcome and represent the number of days where patients were breathing without assistance during the study period. |
| Duration of Weaning | Up to 28 days | Duration of weaning: Time from initiation of weaning until successful extubation |
Countries
United States
Participant flow
Recruitment details
12-2014 to 5/2017, ICU
Participants by arm
| Arm | Count |
|---|---|
| Fentanyl Push First . Fentanyl intravenous (IV) pushes are administered every 5 minutes as needed to target pain and sedation score, up to 4 doses per hour. Every morning 120-min CPAP trial is performed as long as patient's RASS score is 0 to -2 and patient passes the SBT safety screen. If fentanyl IV push doses alone cannot manage patient's pain and agitation (could not reach the target score), notify the study team. Fentanyl infusion is started and titrated to target pain and sedation score up to 6 hours. If fentanyl infusion is titrated up twice consecutively and target pain and sedation score are not met, notify the study team. Propofol infusion is started and titrated to target RASS score up to 6 hours. | 27 |
| Sedation Protocol Without Interruption Continuous infusion of fentanyl and midazolam is started per protocol. Both drugs are titrated to target pain score (0 to 3) using Critical Care Pain Observation Tool (CPOT) and target sedation score (0 to -3) using Richmond Agitation Sedation Scale (RASS). Daily interruption of fentanyl and midazolam is not performed. Every morning 120-min CPAP trial is performed as long as the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen.
Sedation Protocol Without Daily Interruption: Continuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen, 120-min CPAP trial is performed. | 28 |
| Sedation Protocol With Interruption Continuous infusion of fentanyl and midazolam is started per protocol. Both drugs are titrated to target pain score (0 to 3) using Critical Care Pain Observation Tool (CPOT) and target sedation score (0 to -3) using Richmond Agitation Sedation Scale (RASS). Every morning both drugs are stopped (Daily Interruption) and patient's wakefulness is assessed per protocol. If patient's pain and RASS score stays within the target, both drugs are kept off. If patient shows any signs and symptoms of pain or agitation (described in the study protocol), both drugs are restarted at a half dose of the previous dose and titrated to target pain and RASS score. Every morning both drugs are stopped and when patient is awake and met the SBT safety screen, 120-min continuous positive airway pressure (CPAP) trial is performed. | 31 |
| Total | 86 |
Baseline characteristics
| Characteristic | Fentanyl Push First | Sedation Protocol Without Interruption | Sedation Protocol With Interruption | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 15 Participants | 16 Participants | 46 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 13 Participants | 15 Participants | 40 Participants |
| Age, Continuous | 65.6 years STANDARD_DEVIATION 15.8 | 64.1 years STANDARD_DEVIATION 18.4 | 66 years STANDARD_DEVIATION 16.4 | 65.2 years STANDARD_DEVIATION 18.4 |
| Body Mass Index (BMI) Kg/m^2 | 31.5 kg/m^2 STANDARD_DEVIATION 9.9 | 31.2 kg/m^2 STANDARD_DEVIATION 10.1 | 30.3 kg/m^2 STANDARD_DEVIATION 10.3 | 31 kg/m^2 STANDARD_DEVIATION 10.1 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment United States | 27 Participants | 28 Participants | 31 Participants | 86 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 8 Participants | 10 Participants |
| Sex: Female, Male Male | 26 Participants | 27 Participants | 23 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 27 | 6 / 28 | 4 / 31 |
| other Total, other adverse events | 0 / 27 | 0 / 28 | 0 / 31 |
| serious Total, serious adverse events | 1 / 27 | 0 / 28 | 1 / 31 |
Outcome results
Primary
Study Feasibility
Study feasibility for all 3 Arms/Groups (i.e., Fentanyl Push First, Sedation Protocol Without Interruption, and Sedation Protocol with Interruption) being greater than or equal to 80% and protocol feasibility was based on protocol compliance (total percentage of study days participants were compliant with protocol).
Time frame: Up to 28 days
Population: All 3 arms were measure, and the measurement was based on total % of study days where compliant with the respective protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Protocol Compliance | Study Feasibility | 91 Percentage of study days |
| Sedation Protocol Without Interruption | Study Feasibility | 97 Percentage of study days |
| Sedation Protocol With Interruption | Study Feasibility | 93 Percentage of study days |
Secondary
ICU Length of Stay
Duration of ICU stay at 28 days
Time frame: Up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Protocol Compliance | ICU Length of Stay | 7 Days |
| Sedation Protocol Without Interruption | ICU Length of Stay | 7 Days |
| Sedation Protocol With Interruption | ICU Length of Stay | 8 Days |
Other Pre-specified
Duration of Weaning
Duration of weaning: Time from initiation of weaning until successful extubation
Time frame: Up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Protocol Compliance | Duration of Weaning | 2 days |
| Sedation Protocol Without Interruption | Duration of Weaning | 2 days |
| Sedation Protocol With Interruption | Duration of Weaning | 2 days |
Other Pre-specified
Mechanical Ventilation Free Days
This is clinical outcome and represent the number of days where patients were breathing without assistance during the study period.
Time frame: Up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Protocol Compliance | Mechanical Ventilation Free Days | 24 days |
| Sedation Protocol Without Interruption | Mechanical Ventilation Free Days | 23.5 days |
| Sedation Protocol With Interruption | Mechanical Ventilation Free Days | 24 days |